Biotransformation of the sesquiterpene (+)-valencene by cytochrome P450cam and P450BM-3

Org Biomol Chem. 2005 Jan 7;3(1):57-64. doi: 10.1039/b413068e. Epub 2004 Nov 18.

Abstract

The sesquiterpenoids are a large class of naturally occurring compounds with biological functions and desirable properties. Oxidation of the sesquiterpene (+)-valencene by wild type and mutants of P450cam from Pseudomonas putida, and of P450BM-3 from Bacillus megaterium, have been investigated as a potential route to (+)-nootkatone, a fine fragrance. Wild type P450cam did not oxidise (+)-valencene but the mutants showed activities up to 9.8 nmol (nmol P450)(-1) min(-1), with (+)-trans-nootkatol and (+)-nootkatone constituting >85% of the products. Wild type P450BM-3 and mutants had higher activities (up to 43 min(-1)) than P450cam but were much less selective. Of the many products, cis- and trans-(+)-nootkatol, (+)-nootkatone, cis-(+)-valencene-1,10-epoxide, trans-(+)-nootkaton-9-ol, and (+)-nootkatone-13S,14-epoxide were isolated from whole-cell reactions and characterised. The selectivity patterns suggest that (+)-valencene has one binding orientation in P450cam but multiple orientations in P450BM-3.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacillus megaterium / enzymology
  • Bacillus megaterium / metabolism*
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Biotransformation
  • Camphor 5-Monooxygenase / chemistry
  • Camphor 5-Monooxygenase / metabolism*
  • Cytochrome P-450 Enzyme System / chemistry
  • Cytochrome P-450 Enzyme System / metabolism*
  • Mixed Function Oxygenases / chemistry
  • Mixed Function Oxygenases / metabolism*
  • Models, Molecular
  • Molecular Structure
  • NADPH-Ferrihemoprotein Reductase
  • Oxidation-Reduction
  • Pseudomonas putida / enzymology
  • Pseudomonas putida / metabolism*
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / metabolism*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Bacterial Proteins
  • Sesquiterpenes
  • Cytochrome P-450 Enzyme System
  • valencene
  • Mixed Function Oxygenases
  • Camphor 5-Monooxygenase
  • NADPH-Ferrihemoprotein Reductase
  • flavocytochrome P450 BM3 monoxygenases